This pilot study is designed to evaluate the clinical efficacy and safety of transplanted CD34+ hematopoietic stem/progenitor cells (HSC) isolated from mobilized peripheral blood for hematologic reconstitution of patients following myeloablative chemotherapy or radiotherapy. CD34+ HSC are isolated using the Baxter Isolex 300i System, which is a clinical-scale investigational device designed for high through-put enrichment of such cells from mobilized peripheral blood leukaphereses. CD34+ HSC can be used for autologous or allogeneic rescue following intensive cytoreductive therapy. The therapy is targeted to patients with high risk metastatic B-cell malignancies for whom peripheral blood stem cell (PBSC) transplantation is indicated. The objective of the study is to confirm that infusion of highly-enriched CD34+ HSC isolated from mobilized peripheral blood results in hematopoietic reconstitution with no unusual or unexpected toxic side effects. The duration and extent of myelosuppression as well as associated side effects will be documented and reviewed relative to historical controls transplanted with unselected mobilized peripheral blood. The hypothesis of the study is that highly-enriched CD34+ HSC will lead to accelerated hematologic recovery in high risk patients undergoing intensive therapy. To date, CD34+ HSC have been transplanted into six B-cell malignancy patients that have received high-dose preparative cytoreductive therapy. Within 24 hours of cell infusion, G-CSF is started at 5ug/kg/day and is continued until AVC is >1,000/ul for 3 consecutive days. The number of days to neutrophil and platelet recovery is recorded. If engraftment is not documented by day 14-18 following CD34+ HSC infusion, the patients may receive the backup unselected and unmanipulated, PBSC. To date, six of 6 consecutive patients with either multiple myeloma or intermediate grade non-Hodgkin's lymphoma have been successfully engrafted following transplant with highly-enriched (>90%) CD34+ HSC without the need for backup rescue. This study serves as a prelude for planned phase I clinical trials of the use of highly-enriched CD34+ HSC for transplant into breast cancer patients. An IND is currently being prepared for submission to the FDA for expanded clinical use of the Baxter Isolex 300i System beyond B-cell malignancies. In this regard, under NCI/NIH- and U.S. Army Medical/DOD-sponsored grant funding, we will embark on a phase I clinical trial of combining CD34+ HSC transplantation with tumor-pulsed dendritic cell vaccines for the treatment of patients with advanced breast cancer. In addition, a separate planned phase I clinical trial will evaluate the capacity of anti-HER-2/Neu chimeric T cell receptor gene-modified CD34+ HSC to "endow" the developing hematolymphoid progeny lineages post-transplantation with tumor- specificity to target (and potentially eliminate) residual breast cancer cells in patients that overexpress HER-2/Neu (as described in the other "highlights" provided by Dr. Mule).